R Moudry1, S Hornstein1, M Fehr-Bigger1, S Guyer1
1Kantonsspital Graubünden
Background & Objectives: A paediatric patient in our hospital suffers from a rare, hereditary transcobalamin II deficiency resulting in an intracellularvitamin B12 deficiency. Specific treatment consists of massiveparenteral intake of vitamin B12. Parenteral vitamin B12 solution, suitable for children under 3 years of age, is not commercially available in Switzerland. Our aim was to produce a preservative-free, sterile hydroxocobalamin (vitamin B12) solution for intramuscular use and to develop a stability indicating analytical method in order to determine the shelf life of the solution.
Methods: The entire manufacturing process occurred under aseptic conditions. Hydroxocobalamin hydrochloride (Ph.Eur. quality) was dissolvedin NaCl 0.9% to give a concentration of 10 mg /2 ml. The pH value was adjusted to 4.3 – 4.5 using hydrochloric acid. The solution was 0.2 μm filtered and finally, a 2.4 ml solution was aseptically filled in sterilised brown glass vials. The filter integrity was tested using the bubble point method. The vials were kept in the refrigerator. Alternatively, the solution was autoclaved at 121 °C for 15 min and assessed by high performance liquid chromatography (HPLC) for degradation products.
Results: The autoclaved solution showed degradation products and the hydroxocobalamin content was decreased by 20%. In contrast, the sterile filtered solution showed no degradation product and no loss in the hydroxocobalamin content was observed after storage for 24 months at 2 – 8°C. The solution was stable when stored for one month at room temperature and even exposure to 56°C for 2 days did not cause the product to degrade.
Discussion & Conclusions: We produced a hydroxocobalamin solution for intramuscular use with a shelf-life of at least 24 months if refrigerated. The treatment of our patient with this solution, administered as an intramuscular injection once a week, has been extremely successful for more than 3 years.
Poster in: GSASA Mini-Symposium & Assemblée Générale - 25 novembre 2015 - Kongresshaus Zurich
1Kantonsspital Graubünden
Background & Objectives: A paediatric patient in our hospital suffers from a rare, hereditary transcobalamin II deficiency resulting in an intracellularvitamin B12 deficiency. Specific treatment consists of massiveparenteral intake of vitamin B12. Parenteral vitamin B12 solution, suitable for children under 3 years of age, is not commercially available in Switzerland. Our aim was to produce a preservative-free, sterile hydroxocobalamin (vitamin B12) solution for intramuscular use and to develop a stability indicating analytical method in order to determine the shelf life of the solution.
Methods: The entire manufacturing process occurred under aseptic conditions. Hydroxocobalamin hydrochloride (Ph.Eur. quality) was dissolvedin NaCl 0.9% to give a concentration of 10 mg /2 ml. The pH value was adjusted to 4.3 – 4.5 using hydrochloric acid. The solution was 0.2 μm filtered and finally, a 2.4 ml solution was aseptically filled in sterilised brown glass vials. The filter integrity was tested using the bubble point method. The vials were kept in the refrigerator. Alternatively, the solution was autoclaved at 121 °C for 15 min and assessed by high performance liquid chromatography (HPLC) for degradation products.
Results: The autoclaved solution showed degradation products and the hydroxocobalamin content was decreased by 20%. In contrast, the sterile filtered solution showed no degradation product and no loss in the hydroxocobalamin content was observed after storage for 24 months at 2 – 8°C. The solution was stable when stored for one month at room temperature and even exposure to 56°C for 2 days did not cause the product to degrade.
Discussion & Conclusions: We produced a hydroxocobalamin solution for intramuscular use with a shelf-life of at least 24 months if refrigerated. The treatment of our patient with this solution, administered as an intramuscular injection once a week, has been extremely successful for more than 3 years.
Poster in: GSASA Mini-Symposium & Assemblée Générale - 25 novembre 2015 - Kongresshaus Zurich
